EFFECTS OF COCAINE AND FOOTSHOCK STRESS ON EXTRACELLULAR DOPAMINE LEVELS IN THE MEDIAL PREFRONTAL CORTEX

The interaction between cocaine and footshock stress was evaluated by determining changes in extracellular dopamine and metabolite levels by in vivo microdialysis in the medial prefrontal cortex. In the first experiment, rats were given one of three treatments: no pretreatment (naive); or five daily injections of cocaine (1 5 mg/kg, i.p.); or daily saline. Six to seven days later, animals had a microdialysis probe implanted into the medial prefrontal cortex and an acute 20-min footshock stress (0.45 mA/200 ms per s) or sham shock was delivered. The results showed that acute footshock in daily saline pretreated rats increased medial prefrontal cortex extracellular dopamine concentrations to 203% of baseline levels. In rats pretreated with daily cocaine, this stress-induced response was completely abolished and extracellular dopamine was reduced 38% below baseline levels by 100 min post-shock. Naive animals showed a response to footshock that was intermediate between cocaine and saline pretreated rats (156% of baseline). In the second experiment, rats were given either no pretreatment (naive) or five daily 20-min footshock treatments (as above) or daily sham shock. Six to seven days later, an acute cocaine or saline injection was given. In daily sham-pretreated rats, extracellular dopamine levels were increased to 500% of baseline in response to acute cocaine. Pretreatment with daily footshock significantly reduced the response to acute cocaine (216% of baseline). Naive rats showed an intermediate increase that was not significantly different from footshock-pretreated animals (265% of baseline). Locomotor activity measured concurrently with dialysis showed a non-significant trend towards enhanced activity in daily footshock animals. The results indicate that the medial prefrontal cortex does not demonstrate neurochemical cross-sensitization between footshock stress and cocaine, but instead shows apparent tolerance to a challenge following daily footshock or daily cocaine treatment.